Composition, process and use

ABSTRACT

A compound of the general formula ##STR1## or a salt or complex thereof, in which X, Y and Z are all optionally substituted carbon atoms and R is hydrogen, optionally substituted hydrocarbyl or acyl or --COOR 7  and R 7  is hydrocarbyl has anti-microbial properties. Particular examples are compounds in which X is --CH 2  -- or --C(CH 3 ) 2  -- and Y and Z are both --CH 2  -- or X is is --CH 2  -- and Y and Z are carbon atoms of a benzene ring. The zinc complexes have useful properties.

This is a divisional of application Ser. No. 07/555,118, filed on Jul.19, 1990, U.S. Pat. No. 5,120,856.

The present invention relates to a class of compound, a process for thepreparation of such compounds and the use of such compounds asindustrial biocides.

Industrial biocides are useful to prevent industrial spoilage, inparticular that caused by bacteria, fungi and algae. Materials which canbe used as industrial biocides have antimicrobial properties, forexample antifungal, antibacterial or antialgal properties and may evenpossess a combination of properties such as both useful antifungal andantibacterial properties. Such materials are useful in the preservationof products which are susceptible to attack by micro-organisms such asbacteria, fungi and algae. A wide range of products are susceptible toattack by micro-organisms and these products include paints, latices,adhesives, personal care products, leather, wood, plastics materials andadditives to plastics materials, metal working fluids, cooling water andaqueous slurries.

In our European Patent Application Publication No 249328 we disclose abiocide composition which contains at least one compound of the formula##STR2## or a metal complex or salt thereof, the groups A, B and D beingdefined. Many compounds of this type are disclosed. The specificcompounds disclosed are of the type thiazol-thione, imidazolidine-thioneor imidazoline-thione. We have now found that compounds of the typepyrrolidine thione derivatives and pyrroline thione derivatives haveuseful anti-microbial properties.

According to the present invention there is provided a biocidecomposition which contains at least one compound of the formula I:##STR3## or a salt or complex thereof, wherein

X is a group --CR¹ R² -- or a group --CR¹ =;

Y is a group --CR³ R⁴ -- or a group --CR³ =;

Z is a group --CR⁵ R⁶ -- or a group --CR⁵ =;

R is hydrogen, a hydrocarbyl group, a substituted hydrocarbyl group, anacyl group, a substituted acyl group or a group --COOR⁷ ;

R¹ to R⁶ are each, independently, a hydrogen atom, a hydrocarbyl groupor a substituted hydrocarbyl group, or

R¹ and R², together with the carbon atom to which they are attached,form a ring, and/or R³ and R⁴, together with the carbon atom to whichthey are attached, form a ring, and/or R⁵ and R⁶, together with thecarbon atom to which they are attached, form a ring; or

R¹ and R³, together with the carbon atoms to which they are attached,form a ring or R³ and R⁵, together with the carbon atoms to which theyare attached, form a ring; and

R⁷ is a hydrocarbyl group.

The groups X, Y and Z can form part of a further ring system butgenerally not more than two of the groups X, Y and Z form part of afurther ring system. The further ring system is typically a ring systemcontaining five or six atoms and may be a heterocyclic ring system butis preferably a hydrocarbon ring system, for example a cyclopentene,cyclohexane, cyclohexene, cyclohexadiene or benzene ring. The furtherring system, if present, typically contains one or two carbon atoms fromthe groups X, Y, and Z. If only one group forms part of a ring system,this may be a cyclohexane ring of the type ##STR4## where the carbonatom of the group X, Y or Z is the carbon atom with the two freevalencies, which are linked to the other groups in the pyrrolidine orpyrroline ring. If two of the groups X, Y and Z form part of a ringsystem, the further ring is then fused to the pyrrolidine or pyrrolinering system; for example when Y and Z both form part of a ring systemsuch as a benzene ring as in 2-hydroxy-2,3-dihydro-1H-isoindol-1-thione.

Particularly useful biocide compositions in accordance with the presentinvention are those in which the group X is a group --CR¹ R² --, andespecially is a group --CH₂ -- or --C(CH₃)₂ --. The groups Y and Z my begroups --CR³ R⁴ -- or --CR³ = and --CR⁵ R⁶ -- or --CR⁵ = respectively.We have obtained useful biocide compositions using a compound in whichthe groups Y and Z are both --CH₂ -- groups. Useful results have alsobeen obtained when the compound is one in which X is --CH₂ -- and Y andZ together form a benzene ring.

If any of the groups R¹ to R⁶ are substituted groups, the substituentsare typically selected from hydrocarbonoxy groups, acyl groups, ester(that is acyloxy) groups, a halogen atom or a group containing more thanone halogen atom, for example a trifluoromethyl group, or a nitrilegroup.

The group R may be an acyl group, for example an acetyl group (CH₃ CO).However, it is generally preferred that the biocide composition containsa salt or complex of the compound of general formula I. The salt orcomplex may be with an amine (including an alkanolamine) but moretypically is with a metal, which may be any metal. Typically the metalpresent in the salt or complex is a transition metal, for example ametal of group VIII, IB or IIB of the Periodic Table. Such metalsinclude iron, copper and zinc, particularly such metals in their maximumpossible valency state.

All references herein to the Periodic Table are to the Periodic Tableaccording to Mendeleeff, as set out on the inside rear cover of "Generaland Inorganic Chemistry" by J R Partington, Second Edition (1954)published by MacMillan and Co Limited, London.

For convenience hereafter, the compounds of the general formula I, andthe salts and complexes thereof will be referred to simply as "compoundI".

A wide range of compounds I can be used in the biocide compositions ofthe present invention. The compounds I have anti-microbial activityagainst a wide range of micro-organisms including bacteria, fungi andalgae, and have useful anti-bacterial activity. Preferred compounds Ihave a useful combination of anti-bacterial, anti-fungal and anti-algalactivity.

Compounds I which can be used in the compositions of the presentinvention include:

1-acetoxy-2-pyrrolidinthione;

1-acetoxy-5,5-dimethyl-2-pyrrolidinthione; and

2-hydroxy-2,3-dihydro-1H-isoindol-1-thione.

and the metal complexes and salts thereof. The metal salts and complexesthereof include ferric, cupric and zinc complexes and salts.Compositions of the present invention which contain metal salts orcomplexes are preferred, for example compositions which contain one ofthe following complexes:

2:1 complex of 2-hydroxy-2,3-dihydro-1H-isoindol-1-thione and zinc;

2:1 complex of 1-hydroxy-2-pyrrolidinthione and zinc; and

2:1 complex of 5,5-dimethyl-1-hydroxy-2-pyrrolidinthione and zinc.

The biocide composition of the present invention includes a carrier inaddition to compound I. The carrier is typically a material which showslittle, if any, antimicrobial activity and may be, or may include, amaterial which is susceptible to the growth of micro-organisms.

It is generally preferred that the carrier is a liquid medium and thebiocide composition may be a solution, suspension or emulsion ofcompound I in a liquid carrier. The carrier may be water, in which anumber of compounds of formula I, or the salts or complexes thereof, areessentially insoluble. Alternatively , the carrier may be a liquid suchas acetic acid, N,N-dimethylformamide, propylene glycol, dimethylsulphoxide or N-methyl-2-pyrrolidone in which many compounds of formulaI, or the salts or complexes thereof, are soluble. Alternatively, amixture of liquids may be used, one being a solvent for compound I andthe other being a non-solvent, and using such a mixture the compositiontypically comprises an emulsion or droplets of a solution of compound Iin the solvent therefore dispersed in the non-solvent. If a suspensionor emulsion is used, this conveniently contains a surface active agentwhich is effective to maintain the non-continuous phase as a suspensionor emulsion. Any surface active agent known for use in biocidecompositions may be used in such a system, for example alkylene oxideadducts of fatty alcohols, alkyl phenols and amines such as ethylenediamine.

The carrier may be alternatively be a solid when the biocide compositionis very conveniently a solid, particulate material. The solid carriermay be a water-insoluble carrier such as silica or alumina. However, forease of dispersion into a medium to be treated, it is preferred that thecarrier is a water-soluble material since many of the media to betreated are aqueous systems. Any water soluble material may be used as acarrier provided it does not react with, and adversely affect, theantimicrobial properties of compound I. One class of carrier which maybe used in the water-soluble inorganic salts, particularly salt ofmonovalent metals especially the alkali metals. Compound I may bedeposited onto the carrier using any known technique for depositing amaterial from solution onto a solid.

The amount of compound I which is present in the biocide composition maybe just sufficient to have an antimicrobial effect or compound I may bepresent in a substantially greater proportion. It will be appreciatedthat the biocide composition may be provided as a concentrated solutionwhich is subsequently diluted for use as an anti-microbial material.Thus, the amount of the compound I which is present in the biocidecomposition is typically in the range from 0.0001% up to 50% by weightof the biocide composition.

Some of the compounds used in the biocide composition of the presentinvention are new.

Thus, as a further aspect of the present invention there is provided acompound of the formula ##STR5## wherein: X¹ is a group --CR¹ R² -- or agroup --CR¹ =;

Y¹ is a group --CR³ R⁴ -- or a group --CR³ =;

Z¹ is a group --CR⁵ R⁶ -- or a group --CR⁵ =, and R and R¹ to R⁶ are allas herein before defined, with the exceptions that

when X¹ is --C(CH₃)₂ --, R is --H or --CH₃ and Y¹ is --CH₂ --, Z¹ isneither --CH₂ -- nor --C(CH₃)₂ --; and

when X¹ is --C(CH₃)₂ --, R is --H or --CH₃ and Z¹ is --CH₂ --, Y¹ isneither --CH(CH₃)-- nor --CH(C₆ H₅)--.

Preferred compounds in accordance with this further aspect of thepresent invention are those in which the group X¹ is a group --CR¹ R² --and especially is a group --CH₂ --, subject to the exceptions as hereinbefore defined.

As a yet further aspect of the present invention there is provided asalt or complex of a compound of the formula ##STR6## where R, X, Y andZ are all as hereinbefore defined.

In the compounds according to the yet further aspect of the presentinvention, it is preferred that the group X is a group --CR¹ R³ andespecially is a group --CH₂ -- or a group --C(CH₃)₂ --.

The salt or complex is especially one with a metal and materials havinguseful properties have been obtained in which the metal is zinc. Thus,particular materials in accordance with this aspect of the presentinvention are the salt or complex of2-hydroxy-2,3-dihydro-1H-isoindol-1-thione and zinc; the salt or complexof 1-hydroxy-2-pyrrolidinthione and zinc and the salt or complex of5,5-dimethyl-1-hydroxy-2-pyrrolidinthione and zinc.

Compounds of formula I may be prepared in a multi-stage procedurestarting from 1,2 dialdehydes, and the product thus obtained may befurther reacted to obtain a salt or complex if desired. Morespecifically, a dialdehyde is reacted with hydroxylamine to obtain aN-hydroxypyrrolidone or pyrrolinone derivative as an intermediateproduct. The intermediate product is treated with an acid halide such asacetyl chloride to esterify the N-hydroxy group, the esterified productis treated with Lawesson's reagent to obtain the acetyl thione. Thisacetyl derivative, which is a compound of formula I, is preferablyhydrolysed to obtain a hydroxythione compound of formula I. A salt orcomplex is then obtained, if desired, by reaction with a metal salt, forexample zinc acetate.

We have found that some hydroxythione compounds of formula I, that iscompounds in which R is hydrogen, are somewhat unstable and may bedifficult to isolate in a satisfactory yield. We have found that thedesired salt or complex may be obtained directly from the acylderivative by reaction with a trialkylsilanolate of the desired metal.

Thus, as a further feature of the present invention there is provided aprocess for preparing a metal salt or metal complex of a compound offormula I, wherein a trialkylsilanolate of the metal is reacted with acompound of formula I in which the group R is an acyl group.

The trialkylsilanolate is conveniently a trimethylsilanolate. The metalis conveniently zinc. The reaction is conveniently effected in thepresence of a liquid medium which is a solvent for one or both of thereactants but which is preferably a non-solvent, or a poor solvent, forthe desired metal salt or metal complex. A suitable liquid medium istetrahydrofuran but other liquids such as diethyl ether, 1,4-dioxane,toluene, benzene or other aprotic liquids may be used as the liquidmedium. The reaction is conveniently effected at ambient temperature orbelow, for example at 0° C. The reaction is preferably carried out inthe essential absence of moisture for example using dry air or in aninert gaseous atmosphere such as nitrogen or argon.

The reaction product is conveniently insoluble in the reaction mediumand forms a precipitate which can be isolated by any suitable means, forexample by filtration. The process requires only a single stage andgenerally gives a higher yield of the metal salt or metal complex thanis obtained by hydrolysis to form the hydroxy derivative followed byreaction to obtain the metal salt or metal complex.

As an alternative to using butanedial, a 1,2-dialdehyde, as a startingmaterial to obtain 1-hydroxy-2-pyrrolidinone, we have prepared thiscompound from cyclobutanone. More specifically, cyclobutanone is reactedwith N-hydroxybenzenesulphonamide in the presence of a base in asuitable liquid medium. The mixture is acidified to recover the desiredhydroxy compound. The reaction is conveniently effected at ambienttemperature or below, for example at an initial temperature of -10° C.and allowing to warm up to ambient temperature. Any suitable liquidmedium may be used and we have obtained satisfactory results usingaqueous ethanol as the liquid medium.

A convenient process for the preparation of a metal salt or metalcomplex of a compound of formula I comprises the steps of

1) reacting a 1-hydroxy-2-pyrrolidinone or 1-hydroxy-2-pyrrolinonederivative with an acid halide; and

2) reacting the product of step 1 with Lawesson's reagent.

The product of step 2 in the foregoing process is a1-acyloxy-2-pyrrolidinthione compound of formula I. This may be thedesired product but generally it is preferred that the final product isa salt or complex of a compound of formula I. Such a product may beobtained by hydrolysis of the acyloxy compound to obtain thecorresponding hydroxy compound and reacting this hydroxy compound with asalt, particularly a metal salt, to obtain the desired salt or complex.However, as noted previously herein, a salt or complex can be obtainedby reacting the acyloxy compound with a metal trialkylsilanolate and wegenerally prefer to prepare a metal salt or metal complex of thecompound of formula I by reaction of the acyloxy compound with a metaltrialkylsilanolate.

Compound I, typically has anti-bacterial, anti-fungal and anti-algalactivity and preferred Compounds I have useful anti-bacterial,anti-fungal and anti-algal activity. Hence, compound I, or biocidecompositions containing compound I, can be used for the treatment ofvarious media to inhibit the growth of micro-organisms.

As a further aspect of the present invention there is provided a methodfor inhibiting the growth of micro-organisms on, or in, a medium whichcomprises treating the medium with compound I or a biocide compositioncontaining compound I.

Compound I or the biocide composition can be used in conditions in whichmicro-organisms, especially fungi, bacteria and/or algae, grow and causeproblems. Systems in which micro-organisms cause problems includeliquid, particularly aqueous, systems such as cooling water liquors,metal working fluids, geological drilling lubricants, polymer emulsionsand surface coating compositions such as paints, varnishes and lacquersand also solid materials such as wood and leather. Compound I or thebiocide composition can be included in such materials and isparticularly useful when incorporated into a paint, varnish or lacquerto which they provide anti-microbial characteristics.

As a particular aspect of the present invention there is provided asurface coating composition which contains an effective amount ofcompound I

The surface coating composition may be a paint, varnish or lacquer andis especially a paint, for example an emulsion paint. The amount ofcompound I which is present in the surface coating composition istypically in the range from 0.001 up to 2% by weight and especially 0.1up to 1% by weight relative to the total weight of the surface coatingcomposition. Compound I can provide a range of anti-microbialcharacteristics, for example anti-fungal properties, and also anti-algalproperties, to the surface coating composition when applied to a surfaceand can also provide anti-bacterial properties which are useful forin-can preservation of the surface coating composition.

Compound I may be the only antimicrobial compound or may be used in abiocide composition which includes other compounds having antimicrobialcharacteristics. Thus, a mixture of different compounds of formula I, orsalts or complexes thereof, may be used. Alternatively, at least onecompound of the formula I, or a salt or complex thereof, may be usedtogether with one or more known antimicrobial compounds. The use of amixture of anti-microbial compounds can provide a composition having abroader anti-microbial spectrum and hence one which is more generallyeffective than the components thereof. The known anti-microbial may beone possessing anti-bacterial, anti-fungal, anti-algal or otheranti-microbial characteristics. The mixture of compound I with otheranti-microbial compounds typically contains from 1 to 99% by weight,relative to the weight of total antimicrobially active compounds, ofCompound I particularly from 40 to 60% by weight of Compound I.

As examples of known antimicrobial compounds which may be used, togetherwith Compound I, there may be mentioned quarternary ammonium compoundssuch as diethyldodecylbenzyl ammonium chloride;dimethyloctadecyl-(dimethylbenzyl)ammonium chloride;dimethyldidecylammonium chloride; dimethyldidodecylammonium chloride;trimethyl-tetradecylammonium chloride; benzyldimethyl(C₁₂ -C₁₈alkyl)ammonium chloride; dichchlorobenzyldimethyldodecylammoniumchloride; hexadecylpyridinium chloride; hexadecylpyridinium bromide;hexadecyltrimethylammonium bromide; dodecylpyridinium chloride;dodecylpyridinium bisulphate;benzyldodecyl-bis(beta-hydroxyethyl)-ammonium chloride;dodecyl-benzyltrimethylammonium chloride; benzyldimethyl(C₁₂ -C₁₈alkyl)ammonium chloride; dodecyldimethylethyl ammonium ethylsulphate;dodecyldimethyl-(1-naphthylmethyl)ammonium chloride;hexadecyldimethylbenzyl ammonium chloride; dodecyldimethylbenzylammonium chloride and 1-(3-chloroallyl)-3,5,7-triaza-1-azonia-adamatanechloride; urea derivatives such as1,2-bis(hydroxymethyl)-5,5-dimethylhydantoin; bis(hydroxymethyl)urea;tetrakis(hydroxymethyl)acetylene diurea;1-(hydroxymethyl)-5,5-dimethylhydantoin and imidazolidinyl urea; aminocompounds such as1,3-bis(2-ethyl-hexyl)-5-methyl-5-aminohexahydropyrimidine;hexamethylene tetra amine; 1,3-bis(4-aminophenoxy)propane; and2-[(hydroxymethyl)amino]ethanol; imidazole derivatives such as1[2-(2,4-dichlorophenyl)-2-(2-propenyloxy)ethyl]-1H-imidazole;2-(methoxycarbonyl-amino)-benzimidazole; nitrile compounds such as2,4,5,6-tetra-chloroisophthalodinitrile and1,2-dibromo-2,4-dicyanobutane; thiocyanate derivatives such as methylenebis thiocyanate; zinc compounds or complexes such aszinc-2-pyridinethiol-N-oxide; tin compounds or complexes such astributyltin-oxide, chloride, naphthoate, benzoate or 2-hydroxybenzoate;thiazole derivatives such as 2-(thiocyanomethylthio)-benzthiazole; andmercaptobenzthtazole; isothiazole derivatives such as5-chloro-2-methyl-4-isothiazolin-3-one and magnesium salts thereof;2-methyl-4-isothiazolin-3-one; 1,2-benzisothiazolin-3-one and the alkalimetal, ammonium and amine salts thereof; and2-n-octyl-4-isothiazolin-3-one; nitro compounds such astris(hydroxymethyl)nitromethane, 5-bromo-5-nitro-1,3-dioxane and2-bromo-2-nitropropane-1,3-diol; aldehydes and derivatives such asgluteraldehyde (pentanedial) p-chlorophenyl-3-iodopropargyl formaldehydeand glyoxal; amides such as chloracetamide,N,N-bis(hydroxymethyl)chloracetamide, N-hydroxymethyl-chloracetamide anddithio-2,2-bis(benzmethyl amide); guanidine derivatives such as polyhexamethylene biguanide and1,6-hexamethylene-bis[5-(4-chlorophenyl)biguanide]; thiones such as3,5-dimethyltetrahydro-1,3,5-2H-thiodiazine-2-thione; triazinederivatives such as hexahydrotriazine and1,3,5-tri-(hydroxyethyl)-1,3,5-hexahydrotriazine; oxazolidine andderivatives thereof such as bis-oxazolidine; furan and derivativesthereof such as 2,5-dihydro-2,5-dialkoxy-2,5-dialkylfuran; carboxylicacids and the salts and esters thereof such as sorbic acid and the saltsthereof and 4-hydroxybenzoic acid and the salts and esters thereof;phenol and derivatives thereof such as 5-chloro-2-(2,4-dichlorophenoxy)phenol, thio-bis(4-chlorophenol) and 2-phenylphenol; sulphonederivatives such as diiodomethyl-paratolyl sulphone, 2,3,56-tetrachloro-4 (methylsulphonyl) pyridine and hexachlorodimethylsulphone.

Compound I is particularly useful when incorporated into a surfacecoating composition and hence, if used with other compounds havingantimicrobial characteristics, these other compounds are advantageouslycompounds of the type used in surface coating compositions. Compoundswhich may be used in surface coating compositions include, inter-alia,anti-bacterial agents such as imidazolidinyl urea: 1,2-dibromo-2,4-dicyanobutane; 5-chloro-2-methyl-4-isothiazolin-3-one andthe magensium salts thereof; 2-methyl-4-isothiazolin-3-one;1,2-benzisothiazolin-3-one and the salts thereof;2-bromo-2-nitropropane-1, 3-diol; gluteraldehyde; poly hexamethylenebiguanide; triazine derivatives and oxazolidine and derivatives thereof.Surface coating compositions may also include anti-fungal agents such as1[2-(2, 4-dichlorophenyl)-2-(2-propenyloxy) ethyl]-1H-imidazole;2-(methoxycarbonylamino)-benzimidazole;2,4,5,6-tetrachloroisophthalodinitrile; zinc-2-pyridinethiol-N-oxide;2-(thiocyanomethylthio)-benzthiazole; 2-n-octyl-4-thiazolin-3-one;dithio-2, 2-his (benzmethyl amide); diiodomethyl-paratolysulphone and2,3,5,6-tetrachloro-4 (methylsulphonyl) pyridine.

Further aspects of the present invention are described in the followingillustrative examples. In the following tests and examples, all partsare by weight unless stated to the contrary.

In the following examples, the products obtained were subjected tomicrobiostatic evaluation. The microbiological testing was effected,under sterile conditions throughout, as follows:

In the microbiological testing, the products were tested foranti-microbial activity against bacteria and fungi. The bacteria usedwere one or more of Escherichia coli, Pseudomonas aeruginosa,Staphylococcus aureus and Bacillus subtiles. The fungi used were one ormore of Alternaria alternata, Aspergillus niger, Aureobasidum pullulans,Cladosporium sphaerospermum, Cladosporium herbarum, Penicilliumpinophilum, Gliocladium roesum and Chaetomium globosum. Testing againstthe yeast, candida albicans was also carried out in some cases.Anti-algal testing was also carried out as is described in more detailin Examples 13 to 16.

These test organisms will be referred to hereafter as EC, PA, SA, BS,AA, AN, AP, CS, CH, PP, GR, CG and CA respectively.

MICROBIOSTATIC EVALUATION

A) Agar test

The material to be tested was dissolved in a suitable solvent and thesolution obtained diluted with a further quantity of the same solvent togive a desired product concentration.

To a suitable agar medium was added a quantity of the product solutionto give a desired concentration of the product. The agar mediumcontaining the product was poured into petri dish plates and allowed toset.

The test organisms were surface inoculated onto the test plates by meansof a multi-point inoculator. Each test plate was inoculated with bothbacteria and fungi. The plates were incubated for four days at 25° C.

At the end of the incubation period, the plates were assessed visuallyfor growth of the micro-organisms. The concentration of the productwhich inhibited the growth of a particular micro-organism was recorded.

B) Microtitre Assay

A sample of the product to be tested was either dissolved inN,N-dimethylformamide to give a concentration of 5 g. dm⁻³ or, with aproduct which is insoluble in N,N-dimethylformamide, the product isdispersed in water by milling in water for at least 72 hours to give adispersion concentration of 5 g. dm⁻³.

For testing against bacteria, 0.1 cm³ of a fresh stationary phaseculture of the bacterium (having at least 10⁸ cells per cm³) were addedto 100 cm³ of nutrient broth and mixed. 0.1 cm³ aliquots of the mixturewere dispensed into microtitre wells with the exception of the first rowof the plate into which an 0.2 cm³ aliquot was placed. 0.02 cm³ of thesolution or dispersion of the product to be tested was added to thefirst well (which contained an 0.2 cm³ aliquot) and mixed. 0.1 cm³ ofthis mixture was removed, transferred to the well in the adjacent rowand mixed, this serial dilution procedure being effected across theplate until the last well when 0.1 cm³ was discarded. Incubation waseffected for 24 hours at 37° C.

For testing against fungi a similar procedure was used with thefollowing modifications:

A fresh spore suspension of the fungus was made up in sterile saline(this contained 10⁹ cells per cm³) and was used instead of a stationaryphase culture. Malt broth was substituted for nutrient broth. Incubationwas effected for 72 hours at 25° C.

Any precipitation of the compound being tested was noted beforeincubation since precipitation could interfere with assessment of theresults. At the end of the incubation period, the plates were assessedvisually for inhibition of growth of the micro-organisms. Theconcentration of the product which inhibited the growth of a particularmicro-organism was recorded.

EXAMPLE 1 A. Preparation of 2-hydroxy-2,3-dihydro-1H-isoindol-1-one

The procedure was in accordance with the method of O Neunhoeffer and GGottshelch Ann. Chem 1970, (736) 100.

A solution of 13.4 g (0.1 mol) of phthalic dicarboxaldehyde in methanol(30 cm³) was added to a solution of 6.9 g (0.1 mol) of hydroxylaminehydrochloride and 10 g (0.094 mol) of sodium carbonate in water (200cm³).

The mixture was stirred at ambient temperature until reaction wascomplete as determined by thin layer chromatography (tlc) (about 6hours). The solution was washed with chloroform (10 cm³), the pH wasadjusted to seven by the addition of normal hydrochloric acid and theneutral solution was extracted with chloroform (4×40 cm³). The combinedchloroform extracts were chilled to 4° C. overnight to yield a greysolid which was crystallised from a 1:1 by volume mixture of chloroformand diethyl ether. 2-hydroxy-2,3-dihydro-1H-isoindol-1-one having amelting point of 191 - 2° C., was obtained in a yield of 2.38 g (16%).By analysis the product was found to contain C, 64.0% wt., H 4.7% wt.and N 9.3% wt. C₈ H₇ NO₂ requires C 64.4% wt., H 4.7% wt., H 4.7% wt.and N 9.4% wt. The mass spectral data is consistent with the productbeing 2 -hydroxy-2,3-dihydro-1H-isoindol-1-one.

B. Preparation of 2-Acetoxy-2,3-dihydro-1H-isoindol-1-one

2.24 g (15.0 mmol) of 2-hydroxy-2,3-dihydro-1H-isoindol-1-one, obtainedas described in Part A, 1.26 g (15.0 mmol) of sodium hydrogen carbonateand 2.0 g of a 4Å molecular sieve were added to dry dichloromethane (50cm³). The mixture was stirred, cooled on ice and a solution of 3.53 g(45.0 mmol) of acetyl chloride in dichloromethane (20 cm³) was addedover 10 minutes. The solution was allowed to warm to ambient temperatureand, after two hours at ambient temperature, a further 3.53 g (45.0mmol) of acetyl chloride, together with 2.07 g (15.0 mmol) of potassiumcarbonate were added. The resulting mixture was stirred overnight atroom temperature, filtered and evaporated to a crude grey solid.2-acetoxy-2,3-dihydro-1H-isoindol-1-one having a melting point of69°-71° C. was obtained in a yield of 2.62 g (99%). The infra redabsorption spectrum showed peaks at 1800, 1705, 1152, 1003 and 729 cm⁻¹.The mass spectral data is consistent with the product being2-acetoxy-2,3-dihydro-1H-isoindol-1-one.

C. Preparation of 2-hydroxy-2,3-dihydro-1H-isoindol-1-thione

2.33 g (13.2 mmol) of crude 2-acetoxy-2,3-dihydro-1H-isoindol-1-one,prepared as described in Part B, were dissolved in dry dichloromethane(100 cm³), 5.66 g (14.0 mmol) of Lawesson's reagent were added and themixture reluxed for 48 hours, at which time tlc indicated reaction wascomplete. The organic mixture was evaporated to a dark green sludgewhich was dissolved in a mixture of tetrahydrofuran (14 cm³) and water(10 cm³). The mixture was stirred at 50° C. and an aqueous sodiumhydroxide solution was added dropwise to maintain the pH at 8-9. Oncethe pH had stabilised, the aqueous mixture was stirred for a furtherhour before cooling to 0° C. and adding a further quantity of theaqueous sodium hydroxide solution to raise the pH to 10. The basicsolution was washed with diethyl ether (4×50 cm³), acidified with 6 Maqueous hydrochloric acid and extracted with diethyl ether (4× 50 cm³).The combined diethyl ether extracts were washed with water, dried overanhydrous magnesium sulphate and evaporated to an orange oil. This wasflash chromatographed on silica with a petroleum ether (60-80) ethylacetate mixture of varying composition as eluant. The ferric chloridepositive fractions were combined and evaporated. The residue waspurified by dissolving in toluene, adding charcoal, stirring themixture, filtering to remove the charcoal and then crystallising.2-hydroxy-2,3-dihydro-1H-isoindol-1-thione, having a melting point of110-1° C. was obtained in a yield of 0.33 g (15%). By analysis theproduct was found to contain C 58.5% wt. and H 4.3% wt. C₈ H₇ NOSrequires C 58.2% wt. and H 4.2% wt. The infra red absorption spectrumshowed peaks at 1497, 1335, 1290 and 1203 cm⁻¹. The proton n.m.r.spectrum and mass spectral data are consistent with the product being2-hydroxy-2,3-dihydro-1H-isoindol-1-thione.

D. Preparation of 2-hydroxy-2,3-dihydro-1H-isoindol-1-thione zinccomplex (2:1)

200 mg (1.2 mmol) of 2-hydroxy-2,3-dihydro-1H-isoindol-1-thione,obtained as described in Part C, were dissolved in methanol (20 cm³) anda solution of 140 mg (0.6 mmol) of zinc acetate in methanol (20 cm³) wasadded. A grey precipitate appeared. Distilled water (40 cm³) was added,the crude product was collected and then crystallised fromchlorobenzene. 2-hydroxy-2,3-dihydro-1H-isoindol-1-thione zinc complex(2:1) having a melting point of 259° C. was obtained in a yield of 200mg (84%). By analysis the product was found to contain C 48.0% wt., H3.0% wt. and N 6.8% wt. C₁₆ H₁₂ N₂ O₂ S₂ Zn+1% H₂ O requires C 48.3%wt., H 3.15% wt. and N 7.0% wt. The infra red absorption spectrum showedpeaks at 1501, 1297, 1212, 762 and 689 cm⁻ 1. The proton n.m.r. spectrumand mass spectral data are consistent with the product being a 2:1complex.

This material will be referred to as "Compound 1".

EXAMPLE 2 A. Preparation of 1-Hydroxy-2-pyrrolidinone

To a solution of 5.19 g (30 mmol) of N-hydroxybenzenesulphonamide inethanol (30 cm³) at -10° C. (salt ice bath) were added 30 cm³ of a 1 Naqueous solution of sodium hydroxide (30 mmol) with stirring. After 10minutes, 2.1 g (30 mmol) of cyclobutanone were added and the mixture wasstirred at -10° C. for a further one hour. The mixture was allowed towarm up to ambient temperature and left for two days. The mixture wasacidified with 30 cm³ of 1.1 N hydrochloric acid, evaporated and theresidue purified by silica-gel chromatography using ethyl acetate as theinitial eluant, progressively containing a higher proportion ofmethanol, up to 20% methanol by volume. 2.22 g (73% yield) of theproduct were obtained as a syrup. A small sample of this product wascrystallised from toluene and was found to have a melting point of 62°C. By analysis the product was found to contain C 47.0% wt., H 7.8% wt.and N 13.7% wt. C₄ H₇ NO₂ requires C 47.5% wt., H 6.9% wt., and N 13.86%wt. Proton n.m r and C¹³ n.m.r. spectra, and the mass spectral data,were consistent with the product being 1-hydroxy-2-pyrrolidinone.

B. Preparation of 1-Acetoxy-2-pyrrolidinone

To a stirred mixture of 2.0 g (19.8 mmol) of 1-hydroxy-2-pyrrolidinone,prepared as described in Part A, 4.0 g (47.5 mmol) of sodium hydrogencarbonate, 5 g of a 4A molecular sieve and 60 cm³ dry dichloromethane at0° C. were added 9.33 g (0.119 mol) of acetyl chloride. The mixture wasallowed to warm up to ambient temperature and was stirred at ambienttemperature for 24 hours. The mixture was filtered and the liltrateevaporated. The residue of the evaporation was purified by silica-gelchromatography using a 1:1 petroleum ether/ethyl acetate mixture as theinitial eluant, progressively containing more ethyl acetate to 100%ethyl acetate. 2.77 g (982 yield) of the product were obtained as asyrup.

The infra red absorption spectrum showed peaks at 2924, 1797, 1714,1460, 1393, 1359, 1269, 1178 and 1043 cm⁻¹. The proton n.m.r. spectrumwas consistent with the product being 1-acetoxy-2-pyrrolidinone.

C. Preparation of 1-Acetoxy-2-pyrrolidinthione

A mixture of 2.64 g (18.46 mmol) of 1-acetoxy-2-pyrrolidinone, preparedas described in Part B, 7.47 g (18.46 mmol) of Lawesson's reagent and 70cm³ dry dichloromethane was heated under reflux with stirring for fourhours. The mixture was cooled to ambient temperature, and filtered. Thefiltrate was evaporated to dryness and the residue purified twice bysilica-gel chromatography using a mixture of hexane and ethyl acetate aseluant, initially a 2:1 volume mixture containing a progressively higherproportion of ethyl acetate to a 1:1 volume mixture. 2.8 g (95% yield)of the product were obtained as a syrup. The infra red absorptionspectrum showed peaks at 2891, 1793, 1501, 1449, 1420, 1367, 1303, 1276and 1156 cm⁻¹. Proton n.m.r. and C¹³ n.m.r. spectra, and the massspectral data, were consistent with the product being1-acetoxy-2-pyrrolidinthione.

This material will be referred to as "Compound 2".

EXAMPLE 3 A. Preparation of Zinc trimethylsilanolate

100 cm³ of a 0.5 M solution of zinc bromide in dry tetrahydrofuran werecooled to 0° C. and stirred under argon. To this solution were added,dropwise, 100 cm³ of a 1 M solution of sodium trimethylsilanolate in drytetrahydrofuran. The mixture was allowed to warmup to ambienttemperature and was stirred overnight. The mixture was filtered. Thefiltrate was used as a 0.25 M solution of zinc trimethylsilanolate intetrahydrofuran.

B. Preparation of 1-Hydroxy-2-pyrrolidinthione zinc complex (2:1)

To 0.267 g (1.68 mmol) of 1-acetoxy-2-pyrrolidinthione, prepared asdescribed in Part C of Example 2, under argon at 0° C. were added, withstirring, 3.36 cm³ of the solution of zinc trimethylsilanolate intetrahydrofuran obtained in Part A. After 18 hours, a solid product (96mg) was collected by filtration and washed with 5 cm³ oftetrahydrofuran. A further crop of a solid product (50 mg) was obtainedby partial evaporation of the filtrate. The combined solid product(0.146 g, 59% yield) had a melting point of 202° C. By analysis theproduct was found to contain:- C 32.1% wt.; H 4.1% wt. and N 9.2% wt. C₈H₁₂ N₂ O₂ S₂ Zn requires C 32.27% wt., H 4.06% wt. and N 9.41% wt. Theinfra-red spectrum showed peaks at 2948, 1558, 1312, 1151 and 1142 cm⁻¹.Proton n.m.r. and mass spectral data were consistent with the productbeing a 2:1 complex.

This material will be referred to as "Compound 3"

EXAMPLE 4 A. Preparation of 1-Acetoxy-5,5-dimethyl-2-pyrrolidinone

To a stirred mixture of 2.8 g (21.7 mmol) of 5,5-dimethyl-1-hydroxy-2-pyrrolidinone, prepared as described in J. Chem. Soc (1959)pages 2094-2102, 4.38 g (52.1 mmol) of sodium hydrogen carbonate, 7.0 gof 4A molecular sieve and 60 cm³ dry dichloromethane, cooled to 0° C.were added 10.22 g (0.13 mol) of acetyl chloride.

The mixture was allowed to warmup to ambient temperature and stirred atambient temperature for four hours. The mixture was filtered and theliltrate evaporated. The residue of the evaporation was purified bysilica-gel chromatography using a 1:1 volume mixture of petroleum etherand ethyl acetate as the initial eluant, progressively containing moreethyl acetate to 100% ethyl acetate. 3.7 g (100% yield) of the productwas obtained as a syrup. The infra red absorption spectrum showed peaksat 2969, 1794, 1718, 1396 and 1190 cm⁻¹. The proton n.m.r. spectrum wasconsistent with the product being1-acetoxy-5,5-dimethyl-2-pyrrolidinone.

B. Preparation of 1-Acetoxy-5,5-dimethy-2-pyrrolidinthione

A mixture of 3.30 g (20.5 mmol) of1-acetoxy-5,5-dimethyl-2-pyrrolidinone, prepared as described in Part A,8.29 g (20.5 mmol) of Lawesson's reagent and 70 cm³ of drydichloromethane was heated under reflux with stirring for 3.75 hours.The mixture was cooled to ambient temperature and filtered. The filtratewas evaporated to dryness and the residue purified by silica -gelchromatography using a 4:1 volume mixture, changing progressively to a2:1 volume mixture, of petroleum ether and ethyl acetate as eluant. Theproduct was crystallised from a 1:1 petroleum ether/ethyl acetatemixture. 2.65 g (74% yield) of a solid having a melting point of 90°-91°C. were obtained. By analysis the solid product was found to contain C51.5% wt.; H 7.4% wt.; N 7.2% wt. and S 16.9% wt. C₈ H₁₃ NO₂ S requiresC 51.31% wt.; H 7.00% wt.; N 7.4% wt. and S 17.12% wt. The infra redabsorption spectrum showed peaks at 2974; 1800; 1443; 1410; 1366; 1201;1163 and 1078 cm⁻¹. Proton n.m.r. and mass spectral data were consistentwith the product being 1-acetoxy-5,5-dimethyl-2-pyrrolidinthione.

This material will be referred to as "Compound 4".

EXAMPLE 5 A. Preparation of 5,5-Dimethyl-1-hydroxy-2-pyrrolidinthionezinc complex (2:1)

To 1.0 g (5.35 mmol) of 1-acetoxy-5,5-dimethyl-2-pyrrolidinthione,prepared as described in Part B of Example 4, under argon were added,with stirring, 32.1 cm³ of the solution of zinc trimethylsilanolate intetrahydrofuran obtained in Part A of Example 3. The solution of thezinc compound was added in three equal portions over two days (at 0,1and 2 days). After a further day, 1 cm³ of water was added, the mixturewas evaporated and the residue purified by silica-gel chromatographyusing a 9:1 volume mixture, changing progressively to a 2:1 volumemixture, of petroleum ether and ethyl acetate as the eluant. The productwas recrystallised from 1:1 volume hexane-ethyl acetate mixture. 0.55 g(58.5% yield) of a solid product having a melting point of 174°-176° C.was obtained. By analysis the solid product was found to contain C 41.2%wt.; H 6.0% wt.; N 7.3% wt. and S 17.0% wt. C₁₂ H₂₀ O₂ S₂ N₂ Zn requiresC 40.74% wt.; H 5.7% wt.; N 7.9% wt. and S 18.12% wt. The infra redabsorption spectrum showed peaks at 2972, 1546 and 1208 cm⁻¹.

The proton n.m.r. spectrum, and mass spectral data are consistent withthe product being a 2:1 complex.

This material will be referred to as "Compound 5".

EXAMPLE 6 TO 9

The products of Examples 1,3,4 and 5 were evaluated against a range ofmicro-organisms using the procedure of the Microtitre Assay as hereinbefore described. Control of the test organisms was obtained at thelevels set out in the Table One.

                  TABLE ONE                                                       ______________________________________                                        Test                                                                          Or-                                                                           gan-   COMPOUND (b)                                                           ism    1        3       4     5      A     B                                  (a)    (ppm)    (ppm)   (ppm) (ppm)  (ppm) (ppm)                              ______________________________________                                        EC     2        4       <4    1      4     8                                  PA     16       16      125   8      16    32                                 BS     1        1       ND    <0.25  4     2                                  AA     2        4       ND    1      2     31                                 AN     2        16      31    8      2     8                                  AP     4        8       ND    <0.25  1     2                                  CH     8        4       ND    8      1     4                                  CG     4        4       ND    8      1     4                                  ______________________________________                                         Notes to Table One                                                            (a) Organisms are as previously defined herein, the specific strains used     being                                                                         EC NCIB 9132                                                                  PA NCIB 10421                                                                 BS NCIB 1650                                                                  AA PRA F54                                                                    AN CMI 17454                                                                  AP PRA F51                                                                    CH CMI 16203                                                                  CG PRA F55                                                               

(b) 1,3,4 and 5 are Compounds 1,3,4, and 5 as previously defined herein.

A is a complex as obtained in Example 2 of European Patent ApplicationPublication No 249328.

B is a complex as obtained in Example 17 of European Patent ApplicationPublication No 249328.

ND means "Not Determined", the product was not tested against this testorganism.

The lowest level of product tested was 0.25 ppm with the exception ofcompound 4 which was tested to a lowest level of 4 ppm.

EXAMPLES 10 TO 12

The products of Examples 2,3 and 5 were evaluated against a range ofmicro-organisms using the procedure of the Agar test as hereinbeforedescribed. Control of the test organisms was obtained at the levels setout in Table Two.

                  TABLE TWO                                                       ______________________________________                                        Test        COMPOUND (b) (d)                                                  Organism    2       3          5                                              (a) (c)     (ppm)   (ppm)      (ppm)                                          ______________________________________                                        EC          ≦25                                                                            ≦25 ≦25                                     PA          500     ≦25 100                                            SA          ≦25                                                                            ≦25 ≦25                                     BS          ND      ≦25 ≦25                                     AN          500     100        100                                            AP          ≦25                                                                            ≦5  ≦5                                      CS          500     ND         ND                                             AA          ≦25                                                                            ND         ND                                             CG          500     ND         ND                                             GR          ND      ≦5  ≦5                                      PP          ND      ≦5  ≦5                                      CA          ND      >100       >100                                           ______________________________________                                         Notes to Table Two                                                            (a) and (b) are both as defined in Notes to Table One, with the exception     noted in (c) in respect of the test organisms.                                (d) ≦ indicates that the product provided control of the test          organism at the lowest level of product tested.                               > indicates that the product failed to control the test organism at the       highest level of the product tested.                                     

(c) Organisms are as previously defined herein and in Note (a) to TableOne, the strains being:

    ______________________________________                                               EC         NCTC       5934                                                    SA         NCIB       9518                                                    AP         CMI        145194                                                  GR         CMI        260419                                                  PP         CMI        114933                                                  CA         NCYC       597                                              ______________________________________                                    

EXAMPLES 13 TO 16

The products of Examples 1, 3, 4 and 5 were evaluated against an algalmedium using the following procedure:

10 cm³ aliquots of an algal broth medium were placed in test tubes whichwere then capped. A chemical under test was added to the medium to giveconcentrations of from 0.16 ppm to 10 ppm of the chemical.

Each test tube was inoculated with 0.1 cm³ of a mixed algal suspensionwhich was a 7 day culture of a mixture of the following algae:

Stichococcus bacillaris

Gloecapsa alpicola

Nostoc commune

Trentepohlia aurea

The test tubes were incubated at ambient temperature (15°-20° C.) withartificial illumination of between 700 and 1200 LUX provided to give 16hours of illumination and 8 hours of darkness in every 24 hour period.After two weeks, the contents of the test tube were re-inoculated with0.1 cm³ of the mixed algal suspension as described previously.

The incubation with alternate periods of light and dark was continuedfor a period of a further four weeks. The contents of the test tubeswere then assessed visually for algal growth. The concentration of eachchemical which completely inhibited algal growth was noted and theresults are set out in Table Three.

                  TABLE THREE                                                     ______________________________________                                        Ex or            Compound                                                     Comp Ex          Type                                                         (e)              (b)    ppm                                                   ______________________________________                                        13               1      2.5                                                   14               3      2.5                                                   15               4      10                                                    16               5      0.64                                                  C*               NIL    NIL                                                   ______________________________________                                         Notes to Table Three                                                          (b) is as defined in Notes to Table One                                       (e)* Extensive growth of algae was observed with a pronounced green           colouration after seven days.                                            

We claim:
 1. A biocide composition which contains an effective amount ofat least one compound of the formula I: ##STR7## or a salt or complexthereof with a metal of group VIII, IB or IIB of the Periodic Table,together with a carrier material,wherein X is a group --CR¹ R² -- or agroup --CR¹ =; Y is a group --CR³ R⁴ -- or a group --CR³ =; Z is a group--CR⁵ R⁶ -- or a group --CR⁵ =; R is a hydrogen or an acyl group; and R¹to R⁶ are each, independently, a hydrogen atom or a C₁₋₆ -hydrocarbylgroup, or R¹ and R², together with the carbon atom to which they areattached, form a cyclohexane ring, and/or R³ and R⁴, together with thecarbon atom to which they are attached, form a cyclohexane ring, and/orR⁵ and R⁶, together with the carbon atom to which they are attached,form a cyclohexane ring; or R¹ and R^(') together with the carbon atomsto which they are attached, form a benzene ring, or R³ and R⁵, togetherwith the carbon atoms to which they are attached, form a benzene ring.2. The composition of claim 1 wherein X is --CH₂ -- or --C(CH₃)₂ --. 3.The composition of claim 1 which contains a complex with zinc.
 4. Thecomposition of claim 1 which contains at least one compound or onecomplex which is2-hydroxy-2,3-dihydro-1H-isoindol-1-thione/zinc 2:1complex: 1-acetoxy-2-pyrrolidinthione; a1-hydroxy-2-pyrrolidinthione/zinc 2:1 complex;1-acetoxy-5,5-dimethyl-2-pyrrolidinthione; or a5,5-dimethyl-1-hydroxy-2-pyrrolidinthione/zinc 2:1 complex.
 5. Thecomposition of claim 1 wherein the compound of formula I, or a salt orcomplex thereof, is in solution, suspension or emulsion in a liquid. 6.The composition of claim 1 wherein the carrier is a water soluble solidmaterial.
 7. The composition as claimed of claim 1 which contains from0.0001% up to 50% by weight, of the composition, of the compound offormula I or a salt or complex thereof.
 8. A method for inhibition ofthe growth of micro-organisms on, or in, a medium which comprisestreating the medium with a compound of the formula I: ##STR8## or a saltor complex thereof, or with a biocide composition which contains acompound of the formula I or a salt or complex thereof with a metal ofGroup VIII, IB or IIB of the Periodic Table,X is a group --CR¹ R² -- ora group --CR¹ =; Y is a group --CR³ R⁴ -- or a group --CR³ =; Z is agroup --CR⁵ R⁶ -- or a group --CR⁵ =; R is a hydrogen or an acyl group;and R¹ to R⁶ are each, independently, a hydrogen atom or a C₁₋₆-hydrocarbyl group, or R¹ and R² together with the carbon atom to whichthey are attached, form a cyclohexane ring, and/or R³ and R⁴, togetherwith the carbon atom to which they are attached, form a cyclohexanering, and/or R⁵ and R⁶ together with the carbon atom to which they areattached, form a cyclohexane ring; or R¹ and R³ together with the carbonatoms to which they are attached, form a benzene ring, or R³ and R⁵,together with the carbon atoms to which they are attached, form abenzene ring.
 9. The method of claim 8 wherein the biocide compositionor the compound, salt or complex:is incorporated or impregnated into themedium in an amount to provide from 0.001 up to 2% by weight of thecompound, salt or complex relative to the weight of the medium.
 10. Themethod of claim 8 wherein at least one further antimicrobial compound isused.
 11. A biocide composition which contains an effective amount of atleast one compound of the formula I which is a complex with a metal ofgroup VIII, IB or IIB of the Periodic Table: ##STR9## together with acarrier material, wherein X is a group --CR¹ R² -- or a group --CR¹ =;Yis a group --CR³ R⁴ -- or a group --CR³ =; Z is a group --CR⁵ R⁶ -- or agroup --CR⁵ =; R is a hydrogen or an acyl group; R¹ to R⁶ are each,independently, a hydrogen atom or a C₁₋₆ -hydrocarbyl group, or R¹ andR² together with the carbon atom to which they are attached, form acyclohexane ring, and/or R³ and R⁴ together with the carbon atom towhich they are attached, form a cyclohexane ring, and/or R⁵ and R⁶,together with the carbon atom to which they are attached, form acyclohexane ring; or R¹ and R³ together with the carbon atoms to whichthey are attached, form a benzene ring, or R³ and R⁵ together with thecarbon atoms to which they are attached, form a benzene ring.
 12. Amethod for inhibiting the growth of micro-organisms on, or in, a mediumwhich comprises treating the medium with a compound of the formula I:##STR10## or complex thereof with a metal or group VIII, IB or IIB ofthe Periodic Table, or with a biocide composition which contains acompound of the formula I or complex thereof,wherein X is a group --CR¹R² -- or a group --CR¹ =; Y is a group --CR³ R⁴ -- or a group --CR³ =; Zis a group --CR⁵ R⁶⁻⁻ or a group --CR⁵ =; R is a hydrogen or an acylgroup; and R¹ to R⁶ are each, independently, a hydrogen atom or a C₁₋₆-hydrocarbyl group or R¹ and R², together with the carbon atom to whichthey are attached, form a cyclohexane ring, and/or R³ and R⁴, togetherwith the carbon atom to which they are attached, form a cyclohexanering, and/or R⁵ and R⁶, together with the carbon atom to which they areattached, form a cyclohexane ring; or R¹ and R³ together with the carbonatoms to which they are attached, form a benzene ring, or R³ and R⁵,together with the carbon atoms to which they are attached, form abenzene ring.
 13. The composition of claim 1 wherein R is acetyl. 14.The composition of claim 1 wherein the compound is5,5-dimethyl-1-hydroxy-2-pyrrolidinthione as a 2:1 zinc complex.